This invention pertains to herbal extracts, formulations and method for preparing the botanical combinations which can be used for treating AIDS and immune-deficient patients to maintain Kamofsky performance status greater than or equal to 90.
The currently accepted theory of Acquired Immune Deficiency Syndrome (AIDS) involves the loss of the helper cells of the immune system due to infection with the Human Immunedeficiency Virus (HIV). In the advanced stages of the disease, the immune system is rendered helpless in resisting even the normal bacterial flora encountered every day. Eventually, the patient is overcome by bacterial, fungal and viral infections and dies as a result of these opportunistic infections.
Considerable research, therefore, has been aimed at developing synthetic drugs that inhibit one or more stages of the viral life cycle of HIV. Limited success has been achieved by inhibiting the virus-coded reverse transcriptase and protease enzymes. However, a cure for AIDS has not yet been found, and therapy using the nucleoside analogs, although is used currently, has been limited due to many toxic side effects.
While many of the presently synthetic drugs inhibit one or more stages of the viral life cycle of viruses, only a few agents have had any practical value as stated in many pharmacopoeia and textbooks that the specific therapy for viral infections are generally unsatisfactory and thus treatment is primarily symptomatic. Moreover, many of these synthetic drugs show serious systemic adverse effects on various tissues to deteriorate the health even of a normal person. This is also the main reason why a large number of patients currently turn to traditional drugs where the partially purified drug contains mixture of ingredients helps not only suppressing certain pathogenic agents but also promote the well-being of a person that the appetite and body weight are in well-balance. This advantages of traditional drugs are presently realized world-wide and have now been proofed and used clinically especially in Europe, China and many other countries even the real mechanism of action can not yet be delineated.
Thus, there has been a revival in the use of traditional medicine to treat modern disease worldwide. The major source of traditional medicine is in developing countries in which large portions of the populations still rely heavily on indigenous traditional practitioners and local medicinal plants for satisfying their primary health care needs which is, in general, quite self-sufficient. Remedies making use of crude plant materials or their extracts have been handed down through many generations and kept largely secret by traditional practitioners. Continuing efforts to document these formulations are necessary to preserve this information which presently revealed invaluable. Attempts have also been made to improve the formula to give the best therapeutic results.
Herbal remedies have three main advantages over modern synthetic drugs. The first is that their long term use already establishes a certain degree of safety and efficacy in the use of the plant material for human consumption. The second advantage arises out of the use of crude plant materials, which are less costly to prepare than the isolated or synthetic medicinal compounds. In these crude plant materials with many natural components, several compounds in the plant very often act synergistically to increase the effectiveness of the crude plant preparation compared to isolated compounds. The third advantage of the use of medicinal plants is a reduced incidence of adverse drug reactions common to most therapies utilizing synthetic drugs.
The present invention describes formulation and process of making botanical compositions for maintaining Karnofsky score (KS) of 90-100 in immune-deficient patients and especially in AIDS patients. The formulated composition helps maintaining Kamofsky Score (KS) or Kamofsky Performance Scale ranges 90-100 of AIDS patients (vs 100 as of a normal person) with a mean CD4 count of 420 over a 100-week period with slight increase in body weight, where some patients even gain weight significantly. A follow-up result at 100 weeks after treatment using botanical combinations of the present invention shows that all patients are free of opportunistic infections, without undesirable adverse effects and new AIDS-defining event including no developing AIDS dementia complex or other cerebral events and can live a normal life. This is due to the fact that some of the herbal components possesses anti-infectious activity while some has appetite stimulatory effect. These botanical combinations help maintaining Kamofsky score (KS) of 90-100 in all AIDS patients being on the regimen over a 100-week non-comparative clinical trial period although the CD4 count has been shown to increase in only some patients (11 out of 25). This is in great contrast to those patients using didanosine 375 or 250 mg twice daily (for patients weighing  less than 60 kg, n=279) and zidovudine 12 mg/kg/day (n=275) where 73% of patients in each group had experienced a new AIDS-defining event and 40% of patients in each group had died after 80 weeks of treatment (Perry and Noble, 1999). In addition, the cost of the presently described regimen is considerable inexpensive and affordable by the patients. These are contrary to those AIDS patients on very expensive modem regimens whose serious toxic side effects especially bone marrow suppression, abdominal pain, pancreatitis and peripheral neuropathy or lactic acidosis with hepatic steatosis are often the main cause of patient mortality (30-50% ) within a year after starting the therapy despite the fact that reduction in HIV viral load and plasma HIV RNA level have been reported.
Botanical Combination therapies for maintaining Kamofsky score (KS) of 90-100 in AIDS and immune-deficient patients include therapeutic doses of five medicinal plants of Thailand. The first combination drug, ayurvedic composition 1, consists of spray-dried aqueous or aqueous organic solvent extracts of the plant materials Houttuynia cordata, Combretum quadrangulare, Mimusops elengi, Randia siamensis, and Borassus flabellifer in varied amounts 10-300 mg, 10-100 mg, 10-100 mg, 10-100 mg, and 60-600 mg, respectively. The drug mixture is administered in the form of one capsule (100-1,200 mg) twice daily. The second combination therapy consists of ayurvedic composition 1 (one capsule twice daily) plus one 10-500 mg capsule of ayurvedic composition 2 twice daily, where ayurvedic composition 2 is lyophilized or spray-dried powder of aqueous or aqueous organic solvent extract of plant Houttuynia cordata 10-500 mg. Ayurvedic composition 3 consists of dried aqueous or aqueous organic solvent extracts of the plant materials Houttuynia cordata, Combretum quadrangulare, Mimusops elengi, Randia siamensis, and Borassus flabellifer in fixed amounts 32 mg, 20 mg, 20 mg, 20 mg, and 400 mg, respectively. Ayurvedic composition 4 is lyophilized or spray-dried powder of aqueous or aqueous organic solvent extract of plant material Houttuynia cordata in fixed amount, 100 mg. A process for preparing the botanical combinations includes washing, drying and grinding plant materials into powder, extracting the powder by boiling in water, filtering, spray-drying the extract and mixing the dried extracts in defined amount. The process also includes preparing the pharmaceutical dosage forms of the plant extract mixture as hard gelatin capsule which is stored in air-tight containers protected from light and as syrup or tablet or the like.
The therapy presented here for maintaining Kamofsky score (KS) of 90-100 in AIDS and immune-deficient patients makes use of the combinations of botanical drugs. As Kamofsky Score (KS) or Kamofsky Performance Scale is currently accepted to be used in assessment protocols for evaluating an effect of herbal remedy in clinical management of the HIV/AIDS patient as primary end point representing the Degree of Quality of Life (http://www.hivdent.org), the term xe2x80x98good healthxe2x80x99 of the patients referred to in the present description means that such person has been evaluated to have Karnofsky performance status greater than or equal to 90 as he is normal and no complaints, with no evidence of disease or is able to carry on normal activity with minor signs and symptoms of disease. The first is a combination of medicinal plant extracts in measured proportions, ayurvedic composition 1, and the second is a single medicinal plant, ayurvedic composition 2. Ayurvedic composition 1 can be given with or without ayurvedic composition 2, depending on the patient condition. This combination therapy acts by inhibiting opportunistic infections with concurrent stinulation of the immune system. By increasing the body""s ability to fight against various infectious microorganisms, the symptoms associated with AIDS are suppressed or eliminated.
This invention consists of a botanical combination of plant materials, ayurvedic composition 1, in capsule form, as well as a single botanical drug, ayurvedic composition 2, to be used for the purpose of maintaining Karnofsky score (KS) of 90-100 reflecting good health in AIDS and immune-deficient patients, and the process for preparing the same.
This invention, including the aqueous or aqueous organic solvent extracts of Houttuynia cordata, Combretum quadrangulare, Mimusops elengi, Randia siamensis, and Borassus flabellifer, is used for treating to maintain Karnofsky score (KS) of 90-100 in AIDS and immune-deficient patients.
All five plants are grown and harvested all year round where from the three plants, Combretum quadrangulare, Mimusops elengi, and Randia siamensis, stems and branches are used; while the whole plant of Houttuynia cordata and inflorescences of Borassus flabellifer are used. The parts of plant to be used are dried at 60 degree Celsius until constant dry weight is obtained. Each dry ingredient is ground and put through a sieve to obtain powder of uniform particle size. Water is added to cover the powder using approximately 70 liters for 10 Kg dry weight of powder and the mixture is heated until boils for five minutes and simmered at 80 degree Celsius for the next 8 hr. The filtrate is collected and the residual powder is further boiled in 50 liters water and simmered in similar manner twice. All three filtrates are pooled and spray-dried, freeze-dried or concentrating-dried to obtain dried powder extract of each ingredient referred to as dried plant extract. Alternatively, aqueous organic solvent such as ethyl alcohol may also be used instead of water. A similar extraction process is used to extract each plant ingredient to give all the dried plant extracts used in the present invention. The constituents in the dried plant extract of each plant are identified and quantitatively analysed using conventional High Performance Liquid Chromatography. The same method is used to quantify the amount of each plant constituent to be mixed in the pharmaceutical preparations. Furthermore, since the weather does not vary much during the year in the country of plant origin, i.e.xe2x80x94Thailand, where these plants are grown and harvested, there is thus not much difference between the crops harvested at different time of the year regarding the quality and the quantity of the constituents of each plant.
The formulations consist of the following proportions of each plant material:
(i) ayurvedic composition 1 consisting of the dried plant extracts of:
and
(ii) ayurvedic composition 2 consisting of the lyophilized or spray-dried powder of aqueous or aqueous organic solvent extract of plant material in the amount:
Houttuynia cordata 10-500 mg
This invention further relates to the process for preparing the said botanical mixture for maintaining Karnofsky score (KS) of 90-100 in AIDS and immune-deficient patients. The process consists of washing the plant materials Houttuynia cordata, Combretum quadrangulare, Mimusops elengi, Randia siamensis and Borassus flabellifer with water to remove external contaminants, followed by drying and grinding into powder form each of the said botanicals. The powdered materials are then extracted with water or aqueous organic solvent, spray-dried, freeze-dried or concentrating-dried, and then mixed in the following proportions:
(i) ayurvedic composition 1 consisting of dried plant extracts in the amounts:
(ii) ayurvedic composition 2 consisting of the lyophilized or spray-dried powder of aqueous or aqueous organic solvent extract of plant material in the amount:
Houttuynia cordata 10-500 mg
and prepared as pharmaceutical dosage forms.
The total amount of each pharmaceutical dosage form is 100-1,200 mg of the extracts of the said botanical mixture, ayurvedic composition 1, and 10-500 mg of the single botanical drug, ayurvedic composition 2. Both drugs are in the form of hard gelatin capsules. The capsules are stored protected from light in plastic or glass containers with silica gel bags as desiccant, and the openings of the containers are sealed with aluminum foil.
Dosage
One capsule of ayurvedic composition 1 contains the dried extracts of the aforesaid botanicals with a total weight of 100-1,200 mg, and the dosage is one capsule twice daily. One capsule of ayurvedic composition 2 contains 10-500 mg of washed, lyophilized or spray-dried powder of aqueous or aqueous organic solvent extract of plant material Houttuynia cordata, and the dosage is one capsule twice daily. Both dosages may vary according to each individual patient and the advice of a physician.
The presence of HIV in patients"" blood is confirmed by the Elisa and Western Blot assays. Full blown AIDS patients are further identified by the common symptoms of AIDS including the presence of opportunistic infections. The CD4 (helper cells), total lymphocytes, and weight of the patients are monitored during therapy; in addition to performing liver function tests (LFT) and general blood chemistry tests.
One capsule of ayurvedic composition 1 is administered twice daily to confirmed cases of full blown AIDS or HIV positive patients. Ayurvedic composition 2, in the dosage of one capsule twice daily is also given to patients with evidence of TB or opportunistic fungal, viral or bacterial infections. A successful therapy will result in the disappearance of symptoms within three weeks (i.e. disappearance of opportunistic infections), as well as stabilization of body weight. Treatment is then continued to maintain body weight and prevent the return of the symptoms of AIDS. Patients are also given a regimen of multivitamins to ensure proper nutrition.
The dosage may vary according to the advice of a physician. Patients are prohibited from taking any drugs which suppress the immune system; immunesuppressive drugs are contraindicated.